title: Host response to respiratory bacterial pathogens as identified by integrated analysis of human gene expression data.
abstract: Respiratory bacterial pathogens are one of the leading causes of infectious death in the world and a major health concern complicated by the rise of multi-antibiotic resistant strains. Therapeutics that modulate host genes essential for pathogen infectivity could potentially avoid multi-drug resistance and provide a wider scope of treatment options. Here, we perform an integrative analysis of published human gene expression data generated under challenges from the gram-negative and Gram-positive bacteria pathogens, Pseudomonas aeruginosa and Streptococcus pneumoniae, respectively. We applied a previously described differential gene and pathway enrichment analysis pipeline to publicly available host mRNA GEO datasets resulting from exposure to bacterial infection. We found 72 canonical human pathways common between four GEO datasets, representing P. aeruginosa and S. pneumoniae. Although the majority of these pathways are known to be involved with immune response, we found several interesting new interactions such as the SUMO1 pathway that might have a role in bacterial infections. Furthermore, 36 host-bacterial pathways were also shared with our previous results for respiratory virus host gene expression. Based on our pathway analysis we propose several drug-repurposing opportunities supported by the literature.
authors.affiliation: Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America ; Institute for Genome Science, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Smith
authors.forename: Michal
authors.initials: M
authors.lastname: Magid-Slav
authors.forename: James R
authors.initials: JR
authors.lastname: Brown
mesh_terms: D030541:Databases, Genetic; D015870:Gene Expression / Q000235:genetics*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D011008:Pneumococcal Infections / Q000235:genetics; D011552:Pseudomonas Infections / Q000235:genetics; D011550:Pseudomonas aeruginosa; D012333:RNA, Messenger / Q000235:genetics; D012137:Respiratory System / Q000382:microbiology*; D013296:Streptococcus pneumoniae
chemical_list: D012333:RNA, Messenger